Lung Cancer Patients Show Increased Survival When Treated With New Drug

Patients with lung cancer having specific genetic alterations in ALK (Anaplastic Lymphoma Kinase) gene were able to live longer and the spread of the cancer to the brain was prevented when the patients were treated lorlatinib (Lorbrena). Lorlatinib is an anticancer drug which acts by inhibiting Anaplastic Lymphoma Kinase (ALK).

The study was published in New England Journal Medicine.

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‘Lung cancer patients with Anaplastic Lymphoma Kinase (ALK) positive gene have an aggressive cancer. The survival is improved and the risk of metastasis to the brain is reduced by drug Lorlatinib. (Lorbrena)’
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87% of all cases of lung cancer are Non-small-cell lung cancer (NSCLC) out of which 5% cases are of ALK-positive. This type of cancer is very aggressive and it is not associated with smoking. Aggressive cancers are those cancers which grow and spread rapidly.

Investigator Alice Shaw MD, PhD who led the NEJM study said,“When ALK is turned on abnormally, it's like stepping on the gas pedal--it drives uncontrolled proliferation and survival of cancer cells.”

ALK positive patients have a greater risk of developing brain metastasis (spread of cancer) and also tend to be 10-15 years younger than other patients of lung cancer.

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ALK inhibitors which block ALK were discovered in 2008. Justin Gainor, MD, of the Mass General Cancer Center, who worked with Shaw on the study said,“Turning off ALK with an ALK inhibitor is like putting on the brakes. It can lead to rapid killing of cancer cells and cause tumors to shrink dramatically."

Two generations of ALK inhibitors have been developed which include drugs like crizotinib (Xalkori), alectinib (Alecensa), and brigatinib (Alunbrig). The drawback of these drugs is that they were not able prevent relapse and the spread of the cancer to the brain.

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Lorlatinib is a third generation drug of ALK inhibitors and it is very effective at blocking ALK. The FDA has approved it for treating ALK positive cancer patients and even those patients whose cancer continued to progress despite taking older generation ALK inhibitors.

Clinical Trial

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To find out whether lorlatinib prevented the chances of long term remission if it is given as a first line agent in ALK positive patients, a clinical trial was conducted in 23 countries with 296 patients who had advanced and previously untreated ALK positive lung cancer. Half of the patients were given the first line standard of care drug crizotinib which is a first generation ALK inhibitor and the rest of the patients were given lorlatinib.

The results of the study showed that lorlatinib not only reduced the risk of cancer progression and death by 72% but it also reduced the risk of new and recurrent brain metastases by 93%. The side effects of lorlatinib were serious but the most common seen are increase in cholesterol and triglyceride (type of fat) which could be easily controlled by giving appropriate medications which included cholesterol lowering agents.

The investigators will continue this study to determine the long term outcomes. Shaw said,“These results support lorlatinib as a potential first-line option for ALK-positive patients."

Source-Medindia